联合聚乙二醇干扰素α-2a和恩替治疗“e”抗原阳性肝炎:随

StephenW

Oxford Journals
    Medicine & Health
    Clinical Infectious Diseases
    Volume 59, Issue 12
    Pp. 1714-1723.

A Randomized, Open-Label Clinical Study of Combined Pegylated Interferon Alfa-2a (40KD) and Entecavir Treatment for Hepatitis B “e” Antigen–Positive Chronic Hepatitis B

    Qing Xie1,
    Huijuan Zhou1,
    Xuefan Bai2,
    Shuhuan Wu3,
    Jian-Jie Chen4,
    Jifang Sheng5,
    Yao Xie6,
    Chengwei Chen7,
    Henry Lik-Yuen Chan8, and
    Mianzhi Zhao9

+ Author Affiliations

    1Shanghai Ruijin Hospital, Jiao Tong University School of Medicine
    2Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi Province
    3The First Affiliated Hospital of Zhengzhou University, Henan
    4Shanghai Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine
    5The First Hospital, Zhejiang University, Hangzhou
    6Beijing Ditan Hospital
    7People's Liberation Army 85 Hospital, Shanghai
    8Department of Medicine and Therapeutics, The Chinese University of Hong Kong
    9Roche Pharmaceuticals Ltd, Shanghai, China

    Correspondence: Qing Xie, MD, Department of Infectious Diseases, Shanghai Ruijin Hospital, Jiao Tong University School of Medicine, Bldg 36, 197 Ruijin 2nd Road, Shanghai 200025, China ([email protected]).

Abstract

Background. Treatment with pegylated interferon (peg-IFN) alfa-2a (40KD) results in hepatitis B “e” antigen (HBeAg) seroconversion 6 months after treatment in up to 36% of HBeAg-positive chronic hepatitis B patients. This study explored the efficacy of a novel combination of peg-IFN alfa-2a and entecavir (ETV), a potent nucleoside analogue.

Methods. In total, 218 treatment-naive Chinese HBeAg-positive patients were randomized to peg-IFN alfa-2a (180 µg/week) for 48 weeks, either as monotherapy (n = 72), or with 24 weeks of ETV (0.5 mg/daily) added at week 13 (ETV add-on, n = 73), or pretreatment with a 24-week course of ETV, starting peg-IFN alfa-2a at week 21 (ETV pretreatment, n = 73). The primary endpoint was reduction in quantitative HBeAg from baseline to 24 weeks posttreatment.

Results. Significant reductions in HBeAg from baseline were achieved in all treatment groups 24 weeks posttreatment; reductions were comparable across treatment arms (shown as log10 Paul Ehrlich international units [PEIU]/mL): monotherapy: −1.4 (SD, 1.8); ETV add-on: –1.6 (SD, 1.8); ETV pretreatment: –1.3 (SD, 1.7). Rates of HBeAg seroconversion were similar across treatment groups posttreatment (monotherapy: 22 [31%]; ETV add-on: 18 [25%]; ETV pretreatment: 19 [26%]). Significantly greater reductions of hepatitis B virus DNA were achieved with ETV add-on while on treatment, but were not sustained posttreatment. Safety profiles were comparable between treatment groups; adverse events were experienced by 62 (86%) monotherapy, 65 (89%) ETV add-on, and 58 (81%) ETV pretreatment patients.

Conclusions. Neither ETV add-on nor ETV pretreatment demonstrated superiority compared with 48 weeks of peg-IFN alfa-2a monotherapy. The optimal treatment strategy using nucleos(t)ide analogues and peg-IFN alfa-2a remains to be determined.

Clinical Trials Registration. NCT00614471.

StephenW

牛津期刊
    医药与健康
    临床传染病
    第59卷，第12期
    PP。 1714年至1723年。

联合聚乙二醇干扰素α-2a的（40KD）和恩替卡韦治疗乙肝的“e”抗原阳性慢性乙型肝炎的随机，开放标签的临床研究

    清Xie1，
    慧娟Zhou1，
    金学范BAI2，
    书桓WU3，
    健杰Chen4，
    Jifang Sheng5，
    姚Xie6，
    成伟Chen7，
    亨利沥元Chan8和
    绵纸Zhao9

+作者所属机构

    1Shanghai瑞金医院，交通大学医学院
    2Tangdu医院，第四军医大学，西安，陕西省
    郑州大学，河南3The第一附属医院
    4Shanghai曙光医院隶属于中国传统上海中医药大学
    5The第一医院，浙江大学，杭州
    6Beijing地坛医院
    7People解放军85医院，上海
    香港内科及药物治疗的8Department，中国的大学
    9Roche制药有限公司，上海，中国

    函授：清泄，MD，传染病科，上海瑞金医院，交通大学医学院，大厦36，197瑞金二路，上海200025，中国（[email protected]）。

抽象

背景。治疗与聚乙二醇干扰素（PEG-IFN）干扰素α-2a（40KD）导致乙肝的“e”抗原（HBeAg）血清转换治疗6个月后达到36％的HBeAg阳性慢性乙型肝炎患者。本研究探索一种新的PEG-IFNα-2a和恩替卡韦（ETV），一种有效的核苷类似物的组合的功效。

方法。总体而言，218治疗过中国HBeAg阳性患者被随机分配到PEG-IFNα-2a干扰素（180微克/周）48周，无论是作为单药治疗（N =72），或ETV24周（0.5毫克/日线图），在第13周增加（ETV附加，N =73），或ETV的24周的课程预处理，从PEG-IFNα-2a上21周（ETV预处理，N =73）。主要终点是减少从基线24周治疗后的HBeAg定量。

结果。显著减少HBeAg的基线是在所有治疗组24周治疗后实现;减排是整个治疗武器相媲美（如图log10的保罗·埃利希国际单位[PEIU]/毫升）：单药治疗：-1.4（SD1.8）; ETV附加：-1.6（SD1.8）; ETV预处理：-1.3（SD1.7）。 HBeAg血清学转换率分别为类似的各治疗组治疗后（单药治疗：22[31％]; ETV附加：18[25％]; ETV预处理：19[26％]）。乙肝病毒DNA显著降低更多人实现了与ETV插件，而在治疗，但没有持续的治疗后。安全配置文件具有可比性治疗组之间;不良反应62（86％）单药治疗，65（89％）ETV附加，和58（81％），恩替卡韦治疗前的患者经历。

结论。无论ETV附加也不ETV预处理证明优越性48周PEG-IFNα-2a中单药治疗相比。使用核苷（酸）类似物和PEG-IFNα-2a上的最佳治疗策略仍有待确定。

临床试验注册。 NCT00614471。

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组合治疗并不靠谱